Acta Med Scand 1985; 218: 145-7

EDITORIAL

Obesity and Risk of Cardiovascular Disease

In spite of well established associations between obesity and a number of complicating conditions such as hyperinsulinemia, diabetes mellitus, hyperlipidemia and hypertension, all established risk factors for ischemic heart disease, the association between obesity and ischemic heart disease has been enigmatic. Initially, insurance statistics indicated an increased risk of obese subjects to die of heart disease, but, although including a large number of insured lives, these populations consist of selected subjects. Modern, prospec- tive epidemiological studies seemed to support the criticism of insurance statistics, be- cause no association between obesity and cardiovascular disease could be demonstrated (for review, see ref. 1). Nevertheless, the association between obesity and cardiovascular risk factors remained in these studies. If we assume that cardiovascular disease risk factors actually precipitate such diseases, in other words, that a cause-effect relationship does in fact exist, then it is surprising that obese subjects with these risk factors do not frequently suffer from ischemic heart disease, because this is the case with non-obese subjects. Are there protecting factors associated with obesity?

Recent studies seem to have provided results which make this problem easier to understand. First, reports on large epidemiological studies over long periods do indeed show that obesity is an independent risk factor for ischemic heart disease. These studies also indicate that the J-shaped curve of the weight-mortality relationship indicating an increased risk also for the very leanest part of the population, probably can, at least partly, be explained by lean smokers. When the smokers are removed, the increased mortality of the leanest subjects disappears, and there seems to be a continuous increase in mortality with increasing body weight (2). Nevertheless, even if an association now could be found, the fact that a long “incubation time” is needed before cardiovascular disease is precipi- tated in obese populations was still a problem. Very recent work has now probably clarified this enigma.

In principle, the lack of association between obesity and cardiovascular disease could be due to one or more of at least four alternatives. First, risk factors might have no causal relationship with the development of cardiovascular disease, an unlikely alternative. Second, obesity might provide a protecting factor. This factor might be the smaller number of smokers among obese subjects, but this probably does not provide the explanation either. Third, a primary factor could cause both obesity and risk of cardiovascular disease. Overeating might be such a factor. This alternative cannot be totally discarded, because it is known of course that overeating results in obesity, but also in hyperinsulinemia, hyperlipidemia and maybe also hypertension. A final alternative explanation is that only part of the obesity syndrome is associated with risk of cardiovascular disease. If this were correct, then the risk might be so “diluted” in the total obesity population as to be difficult

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to discover. It would, in fact, require long periods of time in large observed populations in order to be disclosed. As will be seen in the following, this is most likely the correct alternative.

Larsson’s thesis (3) examined the risk of ischemic heart disease in relation to obesity in middle-aged men during a 12-year period, and found no association when obesity was expressed in various terms of total body fat. In a reexamination of this material the localization of the enlarged adipose tissue was examined in relation to risk. Simple measurements of waist (W) and hip circumference (H) provided a measurement of abdomi- nal obesity (high W/H ratio), and fortunately these measurements had been performed at the start of this examination. There were clearly increased risks of ischemic heart disease, stroke and total death with increasing abdominal obesity. Particularly striking was the finding that the risk of ischemic heart disease was most pronounced in men with a small amount of total body fat accumulated in the abdominal region, while men with a large total body fat mass, not located primarily in the abdominal region, were at low risk (4). Similar observations have also been made recently among women ( 9 , as well as independently in the Paris prospective study (6).

These studies then show consistently that abdominal obesity is a subgroup of human obesity in which the risk of cardiovascular disease is concentrated. In this subgroup the risk factors are also more pronounced both in prospective and several recent and previous transsectional studies (for references, see ref. 1). Thus, abdominal obesity is the subgroup of obesity which is dangerous.

It is of considerable interest that there are also reasonable possibilities of understanding the pathogenesis of the complications of abdominal obesity. One alternative here is associated with the fact that the adipocytes of the abdominal fat depots are very sensitive to lipolytic stimuli. This means that in stressful situations plasma FFA concentrations often easily reach levels which might have several undesirable consequences. These include an inhibition of glucose transport, and a decreased insulin sensitivity in muscles as well as hypertriglyceridemia via liver synthesis of very low density lipoproteins (for review see ref. 7). An interesting new possible explanation has recently been found. High portal FFA concentrations seem to inhibit liver uptake of insulin, providing a potential explana- tion to peripheral hyperinsulinemia, insulin resistance, diabetes mellitus, hypertriglycer- idemia, and, perhaps in a longer perspective, essential hypertension, in other words the majority of the prevalent complications to abdominal obesity (7).

CONCLUSIONS

These recent advances in the understanding of the “malignant” subgroup of abdominal obesity should also have practical consequences. First, the diagnosis of obesity should include a measurement of the abdominal component. This is easily performed by anyone with a simple measuring tape. When the waist circumference exceeds that of the hip in middle-aged men then the risk of diseases increases steeply. In women the critical ratio is about 0.8. Second, when abdominal obesity is at hand then measurements of a number of complication variables should be made liberally, including plasma insulin and triglycer- ides, glucose tolerance and, of course, blood pressure. Third, treatment of abdominal obesity should be performed on wide indications. Fourth, obesity with other localization, such as in the femoral-gluteal region, is less malignant and should, from a medical view, be considered mainly as a cosmetic problem when present to a moderate extent. Treatment is not urgent in this condition.

Per Bjijrntorp, Department of Medicine I, Sahlgren’s Hospital, University of Goteborg, S-423 45 Goteborg, Sweden

Acta Med Scand 1985; 218 Editorial 147

REFERENCES I . Larsson B, Bjorntorp P, Tibblin G . The health consequences of moderate obesity. Int J Obesity

2. Gamson RJ, Feinleib M, Castelli WP, McNamara PM. Cigarette smoking as a confounder of the relationship between relative weight and long-term mortality in the Framingham study. JAMA 1983; 249: 2199-203.

3. Larsson B. Obesity-a population study of men, with special reference to development and consequences for the health. University of Goteborg, 1978. Thesis.

4. Larsson B, Svardsudd K, Weiin L, Wilhelmsen L, Bjorntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J 1984; 288: 1401-4.

5. Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, Sjostrom L. Distribution of adipose tissue and risk for cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenburg, Sweden. Br Med J 1984; 289: 1257-61.

6. Ducimetiere P, Avons P, Combien F, Richard J-L. Corpulence history and fat distribution in CHD etiology. The Paris Prospective Study. Eur Heart J 1983; 4 (Suppl E): 8.

7. Bjorntorp P. Hazards in subgroups of human obesity. Eur J Clin Invest 1984; 14: 239-41.

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